PMID- 10353696 OWN - NLM STAT- MEDLINE DCOM- 19990803 LR - 20190921 IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 11 IP - 3 DP - 1999 Mar TI - Activation of protein kinase A by dibutyryl cAMP treatment of NIH 3T3 cells inhibits proliferation but fails to induce Ser-133 phosphorylation and transcriptional activation of CREB. PG - 211-9 AB - The cAMP analogue dibutyryl cAMP (dbcAMP) is often used to activate the protein kinase A pathway and to study the expression of cAMP-responsive genes. Here we show that in NIH 3T3 cells dbcAMP is able to activate PKA, but fails to stimulate expression of the cAMP-inducible c-fos gene. Co-expression of A-kinase anchoring protein 75, previously shown to amplify cAMP signalling and to stimulate c-fos expression, could not restore cAMP responsiveness of the c-fos promoter. DbcAMP-induced activation of PKA may result in poor translocation of the catalytic sub-units of PKA to the nucleus, indicated by the lack of both Ser-133 phosphorylation of the cAMP-response element binding factor CREB and stimulation of the transcriptional activity of this factor. DbcAMP treatment, however, inhibited cell proliferation. These results suggest that cAMP-mediated inhibition of proliferation may be independent of translocation of the catalytic sub-units into the nucleus. FAU - Seternes, O M AU - Seternes OM AD - Department of Gene Biology, Institute of Medical Biology, University of Tromso, Norway. FAU - Sorensen, R AU - Sorensen R FAU - Johansen, B AU - Johansen B FAU - Moens, U AU - Moens U LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 1F7A44V6OU (Colforsin) RN - 452VLY9402 (Serine) RN - 63X7MBT2LQ (Bucladesine) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - 3T3 Cells MH - Animals MH - Bucladesine/*metabolism MH - Colforsin/pharmacology MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Cyclic AMP-Dependent Protein Kinases/*physiology MH - Dose-Response Relationship, Drug MH - Mice MH - Phosphorylation MH - Proto-Oncogene Proteins c-fos/metabolism MH - Serine/*metabolism MH - Signal Transduction MH - Time Factors MH - *Transcriptional Activation EDAT- 1999/06/03 00:00 MHDA- 1999/06/03 00:01 CRDT- 1999/06/03 00:00 PHST- 1999/06/03 00:00 [pubmed] PHST- 1999/06/03 00:01 [medline] PHST- 1999/06/03 00:00 [entrez] AID - S0898-6568(98)00069-2 [pii] AID - 10.1016/s0898-6568(98)00069-2 [doi] PST - ppublish SO - Cell Signal. 1999 Mar;11(3):211-9. doi: 10.1016/s0898-6568(98)00069-2.